NM_014140.4(SMARCAL1):c.1975C>T (p.Arg659Cys) AND Schimke immuno-osseous dysplasia

Clinical significance:Uncertain significance (Last evaluated: Oct 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001305151.1

Allele description [Variation Report for NM_014140.4(SMARCAL1):c.1975C>T (p.Arg659Cys)]

NM_014140.4(SMARCAL1):c.1975C>T (p.Arg659Cys)

Gene:
SMARCAL1:SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a like 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_014140.4(SMARCAL1):c.1975C>T (p.Arg659Cys)
HGVS:
  • NC_000002.12:g.216450969C>T
  • NG_009771.1:g.43556C>T
  • NM_001127207.2:c.1975C>T
  • NM_014140.4:c.1975C>TMANE SELECT
  • NP_001120679.1:p.Arg659Cys
  • NP_054859.2:p.Arg659Cys
  • LRG_108:g.43556C>T
  • NC_000002.11:g.217315692C>T
  • NM_001127207.1:c.1975C>T
Protein change:
R659C
Molecular consequence:
  • NM_001127207.2:c.1975C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014140.4:c.1975C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Schimke immuno-osseous dysplasia (SIOD)
Synonyms:
Spondyloepiphyseal dysplasia nephrotic syndrome; Schimke syndrome; Schimke immunoosseous dysplasia
Identifiers:
MONDO: MONDO:0009458; MedGen: C0877024; Orphanet: 1830; OMIM: 242900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001494473Invitaecriteria provided, single submitter
Uncertain significance
(Oct 9, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Massively parallel sequencing and targeted exomes in familial kidney disease can diagnose underlying genetic disorders.

Mallett AJ, McCarthy HJ, Ho G, Holman K, Farnsworth E, Patel C, Fletcher JT, Mallawaarachchi A, Quinlan C, Bennetts B, Alexander SI.

Kidney Int. 2017 Dec;92(6):1493-1506. doi: 10.1016/j.kint.2017.06.013. Epub 2017 Aug 23.

PubMed [citation]
PMID:
28844315

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001494473.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with cysteine at codon 659 of the SMARCAL1 protein (p.Arg659Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs148893764, ExAC 0.01%). This variant has been observed in individual(s) with focal segmental glomerulosclerosis (PMID: 28844315). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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